The prospects for Near Infrared (NIR) spectroscopy and imaging of the breast for detection, characterization, and monitoring of disease continue to appear promising. The technology is particularly attractive in this setting because it offers low-cost, non-ionizing exposures, very high intrinsic contrast for'pathology and images of functional information associated with physiological and compositional tissue changes. During the current funding period Project IV, Near Infrared Spectroscopy and Imaging, has realized an NIR,imaging system that creates quantitative maps of hemoglobin concentration, oxygen saturation, water content and scattering parameters in vivo. The system is clinically operational, collects three-dimensional, multi-spectral optical data and produces two and three-dimensional images of the breast volume of interest. It has been used to deliver well over 100 clinical exams ? data which has been analyzed to (i) establish normative responses in breasts without disease (ii) explore optical property variations with menstrual cycle and changes in breast compression at time of exam, (iii) estimate NIR image contrast in breasts with screening abnormalities, and (iv) correlate NIR imaged parameters with pathological markers identified through histology. The proposal for continuation of Project IV builds on this foundation in several significant ways through a research plan that consists of both technical and clinical advances. Technically, it will extend the spectroscopy and imaging systems available through incorporation of both hardware and software based coregistrations with MR (Magnetic Resonance) and wideband spectral acquisitions through both full-field optical arrays and localized point spectroscopy probes. Clinical involvement will not only include continued NIR imaging of screening abnormalities recommended for biopsy but also extend to larger palpable masses on clinical breast exams and locally advanced breast cancers receiving neoadjuvant therapy, the long-term goal of this research is to determine the likely role of NIR breast imaging for risk assessment, early detection, differential diagnosis, treatment prognosis and therapy monitoring, It is expected that sufficient evidence will be generated during the requested funding period to allow convincing estimates of the potential of NIR breast imaging as an alternative for differential diagnosis, and pilot data in support of a role in treatment prognosis and therapy monitoring which would inform decisions on the initiation of multi-center trials with the technology in the future.